AB0887 THE EFFECTIVENESS AND SAFETY OF MESENCHYMAL STEM CELLS IN TREATMENT OF SYSTEMIC SCLEROSIS: SYSTEMATIC REVIEW
Authors: L. Zaripova, Z. Bekniyazova, E. Insibayeva, A. Kambar, N. Imanbaeva, S. Tuganbekova
Journal: Annals of the Rheumatic Diseases (2023)

<h3>Background</h3> Systemic scleroderma, or systemic sclerosis (SSc) is an autoimmune disease with high morbidity and mortality, characterised by fibrosis of the skin and internal organs. In the last decade, alternative methods of treatment of SSc resistant to standard immunosuppressive therapy have been actively studied. Of interest are the data about mesenchymal stem cells (MSCs) with their immunomodulatory properties, the ability to self-renew and differentiation. <h3>Objectives</h3> to evaluate the safety and effectiveness of MSCs transplantation in SSc refractory to standart therapy by a systematic review. <h3>Methods</h3> The search was conducted on PubMed and Google Scholar platforms using the following strategy: "Systemic sclerosis" + "Mesenchymal stem cells". All articles presented in the public domain published before 01.12.2022 in the format of case descriptions, clinical and multicenter studies (Case Reports, Clinical Studies, Clinical Trials, Multicentre Studies) were analyzed. The effectiveness of MSCs was evaluated using the index of systemic sclerosis activity and the modified Rodnan skin score (mRSS), diffusing Capacity of the lungs for carbon monoxide (DLCO), the Mouth Handicap in Systemic Sclerosis (MHISS), the Cochin Hand Functional Disability Scale (CHFS),left ventricular ejection fraction (LVEF), EASTAR 2017 Disease Activity Index, visual analog scale (VAS), manifestations of Raynaud's syndrome, laboratory parameters (ESR, CRP), immunological parameters (ANA, Scl-70). The safety assessment included the registration of various adverse events during and after transplantation. <h3>Results</h3> For the period from 2010-2022, fifty publications were found on the topic of MSCs transplantation in SSc, of which 15 publications met the above criteria and were included in the study. The data of 417 patients who underwent transplantation of MSCs obtained from various biological sources (bone marrow - 7, adipose tissue - 5, umbilical cord - 1) were analyzed. The average age of the patients was 42.42 ± 10.79 y.o. The results obtained suggested that there was a significant decrease in the activity of SSc compared to the baseline level of mRSS scale from 21.81± 7.2 to 4.5 ± 5.4, the number of finger ulcers decreased, there was an improvement in mouth opening assessed by the MHISS scale, 2.5 fold decrease in the level of Scl-70, and 2-fold decrease in VAS (<i>p</i>=0.05). The assessment of all patients (n=417) who underwent MSCs transplantation revealed a few side effects, such as postoperative consequences (bruising, swelling and soreness of the donor site, resolved within 14 days), a superficial wound infection (1 patient), which succumbed to oral antibacterial therapy and no further surgical intervention was required. Pulmonary hypertension was diagnosed in 5 patients 24 months after MSCs transplantation; ventricular arrhythmias requiring treatment with carvedilol was observed in 1 patient four months after MSCs transplantation. Restrictive cardiomyopathy and chronic fibrosing myocarditis developed in 1 patient. 6 patients who underwent liposuction had transient paresthesia, which was completely eliminated after a few weeks; 1 patient dropped out due to dizziness after lidocaine injection. 2 patients complained about digital ulcers developed within 24 months. No tumor-related events were observed. The mortality rate consisted in 1.19%, the survival rate was 98.81%. Cause of death (5 cases in total): pneumonia- 1, lung cancer- 1, unknown – 2 patients. One patient died from sudden cardiac arrest due to ventricular fibrillation. <h3>Conclusion</h3> According to the analysis of data from different up-to-date research, MSCs transplantation in SSc patients improved the degree of skin thickening, lung function and mouth opening, as well as relieved ulcers and finger pain without serious side effects. Thus, MSCs can be suggested as an effective and promising therapeutical approach for patients with SSc resistant to standard immunosuppressive therapy. <h3>REFERENCES:</h3> NIL. <h3>Acknowledgements:</h3> NIL. <h3>Disclosure of Interests</h3> None Declared.